DRACULA1 Partum Depression: an Integrated Molecular-pharmaco-imaging Study")

Post-partum Depression Clinical Trial

Official title:

("The Role of the Glutamatergic Neurotransmission in Post- Partum Depression: an Integrated Molecular-pharmaco-imaging Study")

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06131255
• Other study ID #: DRACULA 1
• Status: Not yet recruiting
• Start date: January 1, 2024
• Est. completion date: April 30, 2026

Study information

• Verified date: March 2023
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Domenica mercadante, doctor
• Phone: 02 5503 2234
• Email: domenica.mercadante[@]policlinico.mi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Post-partum depression (PPD) is a prevalent subtype of major depressive disorder that causes a significant distress to the woman and substantial impact on the whole family. Many studies implicate the glutamatergic system in pathological processes relevant to PPD disorders. There is evidence that cell adhesion molecules (CAMs) play a key role in how glutamatergic circuits wire up during development and how glutamatergic synapses, once formed, operate. However, it is unclear how dysregulation in diverse CAMs alter glutamatergic circuitries responsible for emotional and social behavior.

Here, the investigators propose to evaluate the molecular and neurobiological underpinnings of PPD focusing on CAMs at glutamatergic synapses by using an integrated approach from mouse models to human patients. Moreover, the investigators will also perform a pilot study to investigate the impact of selective antidepressants, known to be linked to CAMs, in both human and mice.

Description:

Patients will be recruited by the physician in charge of the study or collaborators of the S.C. Neonatology and Neonatal Intensive Care Unit of the IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation upon referral from the S.C. Psychiatry of the same institution. In the study, exposure to citalopram treatment will be 12 weeks with follow-up every 4 weeks. At each participant, at the time of enrollment, will be assigned a unique code so that only the local investigators can trace the subject's identity. As part of a scheduled visit to assess the clinical diagnosis, the PPD patient will be offered to participate in the study, after the appropriate signing of informed consent, the verification of absence of criteria for exclusion and existence of the study inclusion criteria. If these criteria are met, some demographic and clinical medical history of the women with PPD will be collected, as already provided by clinical practice for the management of the disease. Patients will undergo MRI scanning at baseline at the S.C. Neuroradiology of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and will begin the pharmacological treatment with citalopram. It is emphasized that the administration of citalopram therapy for the treatment of depressive symptomatology will be proposed and carried out in the patient due to clinical needs, based on the judgment of the competent physician and as would already be the case in practice, thus completely independent of participation or non-participation in the present study. Neuroimaging data will be obtained with a Philips 3T magnetic resonance imaging MRI machine. For each patient enrolled in the study, a structural T1 sequence (3D MPRAGE) is acquired.

T1-weighted MRI images will be used to study the differences brain morphology, including the volumes of gray matter (GM) and white matter (WM) and voxel-based morphometry. In a comparison parallel between regions of interest (ROIs), regional volumes will be estimated using the automated anatomical labeling atlas (AAL) as a reference, with emphasis on the dorsolateral PFC (DL)/ventrolateral (VL), cingulate cortex, amygdala and hippocampus. Further regional analysis will allow estimation, in addition to cortical volumes and subcortical volumes, cortical thickness, cortical surface area, and the cortical gyrification of the Desikan-Killiany atlas regions. During treatment with citalopram, patients will be visited, as per standard clinical practice, every 4 weeks. At each of these follow-up visits will be administered to patients by medical specialists the Brief Psychiatric Rating Scale (BPRS) and the Hamilton Depression Rating Scale (HAM- D) to study symptomatology depression. Patients will be, instead, self-administered in Italian language the Maternal Postnatal Attachment Scale (MPAS) and the Parental Stress Index (PSI) to investigate mother-child attachment and parental stress. The time scheduled for completion of both scales will be about 40 minutes. At 12 weeks, as per practice, the MRI scan will be repeated at the S.C. Neuroradiology Department of the Foundation. The following variables will be collected as part of this study: socio-demographic variables (age, schooling, socio-economic);

• clinical/anamnestic variables (age of onset, duration of untreated treated, drug therapy, comorbidities, familiarity, substance abuse/dependence);

• BPRS and HAM-D scales scores for symptomatology assessment (T0, T1, T2, T3);

• MPAS and PSI scales scores for the assessment of mothers child attachment. (T0, T1, T2, T3);

• MRI scan data (T0, T3): the images will be used to study brain morphological differences, including GM and WM volumes, and voxel-based morphometry. In a parallel comparison between regions of interest (ROI), regional volumes will be estimated using as a reference the automated anatomical labeling atlas (AAL), with particular attention to the dorsolateral (DL)/ventrolateral (VL) PFC, cingulate cortex, amygdala and hippocampus. A further regional analysis will make it possible to estimate, in addition to cortical and subcortical volumes, the thickness cortical, cortical surface area and cortical gyrification of the Desikan-Killiany atlas regions.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: April 30, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 40 years;

• female gender;

• PPD diagnosed by DSM-5 structured clinical interview support (SCID-5) by trained medical personnel;

• comorbidity with metabolic syndrome, which can lead to brain damage and cognitive flaws;

• need to start citalopram therapy for clinical needs (and therefore independent of study participation) or already on therapy for no more than two weeks;

• moderate to severe depression according to the 17-item HAM-D (score 14-24);

• absence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;

• Absence of concomitant psychiatric therapies (antidepressants, antipsychotics of the first and second generation and mood stabilizers);

• absence of contraindications for MRI scanning;

• patients who have signed informed consent.

Exclusion Criteria:

• age below 18 years or above 40 years;

• diagnosis different from PPD based on SCID-5;

• absence of metabolic syndrome;

• low depression according to the 17-item HAM-D (score less than 14);

• presence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;

• presence of concomitant drug therapies (antidepressants, first- and second-generation antipsychotics and mood stabilizers);

• presence of contraindications for MRI scanning;

• presence of contraindications for citalopram;

• patients who have not signed informed consent.

Related Conditions & MeSH terms

• Depression
• Depression, Postpartum
• Depressive Disorder
• Post-partum Depression

Intervention

Drug:
• Citalopram
Patients will be administered citalopram, regardless of inclusion or non-inclusion in this study, on medical indication, as per normal clinical practice for disease management and according to the Summary of Product Characteristics (SPC). Patients will have two MRI scans done (at baseline and at 12 weeks after the start of therapy) to assess: brain volumetry, tissue amount of gray matter - GM - and white matter - WM

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico	Milan	MI

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Country where clinical trial is conducted

Italy, 

References & Publications (8)

Asahina H, Masuba A, Hirano S, Yuri K. Distribution of protocadherin 9 protein in the developing mouse nervous system. Neuroscience. 2012 Dec 6;225:88-104. doi: 10.1016/j.neuroscience.2012.09.006. Epub 2012 Sep 11. — View Citation

Bambico FR, Belzung C. Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis? Curr Top Behav Neurosci. 2013;15:243-91. doi: 10.1007/7854_2012_234. — View Citation

Boku S, Nakagawa S, Toda H, Hishimoto A. Neural basis of major depressive disorder: Beyond monoamine hypothesis. Psychiatry Clin Neurosci. 2018 Jan;72(1):3-12. doi: 10.1111/pcn.12604. Epub 2017 Oct 19. — View Citation

Bruining H, Matsui A, Oguro-Ando A, Kahn RS, Van't Spijker HM, Akkermans G, Stiedl O, van Engeland H, Koopmans B, van Lith HA, Oppelaar H, Tieland L, Nonkes LJ, Yagi T, Kaneko R, Burbach JP, Yamamoto N, Kas MJ. Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development. Biol Psychiatry. 2015 Oct 1;78(7):485-95. doi: 10.1016/j.biopsych.2015.01.017. Epub 2015 Feb 7. — View Citation

Cingolani LA, Thalhammer A, Yu LM, Catalano M, Ramos T, Colicos MA, Goda Y. Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta3 integrins. Neuron. 2008 Jun 12;58(5):749-62. doi: 10.1016/j.neuron.2008.04.011. — View Citation

Davis AD, Hassel S, Arnott SR, Harris J, Lam RW, Milev R, Rotzinger S, Zamyadi M, Frey BN, Minuzzi L, Strother SC, MacQueen GM, Kennedy SH, Hall GB. White Matter Indices of Medication Response in Major Depression: A Diffusion Tensor Imaging Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Oct;4(10):913-924. doi: 10.1016/j.bpsc.2019.05.016. Epub 2019 Jun 12. — View Citation

Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L, Duman RS. Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol. 2013 Feb;16(1):69-82. doi: 10.1017/S1461145712000016. Epub 2012 Feb 17. — View Citation

Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. Heterogeneity of postpartum depression: a latent class analysis. Lancet Psychiatry. 2015 Jan;2(1):59-67. doi: 10.1016/S2215-0366(14)00055-8. Epub 2015 Jan 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess the tolerability profile of the drug in the same patients	Evaluation of the serious and nonserious adverse events number judged by the medical staff to be related to the drug under study.	12 weeks
Primary	Evaluate the citalopram effect on white matter morphology	Any statistically significant changes in brain volumetry and in the tissue amount of white matter (WM) will be evaluated after 12 weeks of treatment with citalopram.	12 weeks
Primary	Evaluate the citalopram effect on gray matter morphology	Any statistically significant changes in brain volumetry and in the tissue amount of gray matter (GM) will be evaluated after 12 weeks of treatment with citalopram.	12 weeks
Secondary	To evaluate the efficacy of citalopram on the clinical symptomatology of the PPD patients through the use of clinical scales	Variation of the score of HAM-D for measuring patients' symptomatology after 12 weeks after the start of treatment. Patients will be considered responsive if they have at least a 30% reduction from baseline HAM-D baseline after 12 weeks of treatment with citalopram.	12 weeks